      Document 0196
 DOCN  DRG0196
 UNIQUE IDENTIFIER        DRG-0051
 NAME OF SUBSTANCE        3'-Azido-2',3'-dideoxyuridine [USP DI 1995]
 REGISTRY NUMBER          84472-85-5
 STANDARD CHEMICAL NAME   3'-Azido-2',3'-dideoxyuridine [CHEMLINE]
 SYNONYMS                 Azidouridine [AmFAR Tx Dir Dec 1988]
 SYNONYMS                 AzdU [Int Conf AIDS. 1990 Jun 20-23;6(3):
                          (abstract no. S.B. 483)]
 SYNONYMS                 AzUrd [AmFAR Tx Dir Dec 1988]
 PROTOCOL ID NUMBERS      NIAID 89 CC-62
 IND NUMBER               33086
 SECONDARY SOURCE ID      CS-87 [AmFAR Tx Dir Dec 1988]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: (Human data unavailable).
                          Inhibits HIV replication by inhibiting
                          reverse transcriptase. In peripheral blood
                          mononuclear cells, the major metabolite of
                          3'-azido-2',3'-dideoxyuridine (AzdU) is
                          AzdU-5' monophosphate.  It is believed that
                          this monophosphate becomes di- and
                          triphosphorylated by cellular enzymes.
                          Triphosphorylated AzdU interferes with the
                          RNA-dependent DNA polymerase (reverse
                          transcriptase) of several retroviruses,
                          including HIV, and thus inhibits HIV
                          replication preventing cDNA synthesis. Like
                          zidovudine (azidothymidine (AZT)), it
                          inhibits cellular DNA polymerase alpha;
                          however, concentrations of AzdU that inhibit
                          cellular DNA polymerase are 3000 to 5000-fold
                          greater than those required to inhibit HIV
                          reverse transcriptase. In various cell-virus
                          systems, the activity of AzdU varied from
                          system to system: The anti-viral activity of
                          AzdU in peripheral blood mononuclear (PBM)
                          and MT-4 cell cultures was 100 times less
                          than that of AZT, regardless of the type of
                          retrovirus used; in HeLa-T4 cell cultures,
                          AZT was only 3.5 times more active than AzdU;
                          in ATH8 cells, AzdU and AZT inhibited
                          HIV-induced CPE equally well; in human
                          monocytes and macrophages, AzdU was 10-20
                          times more active than in PBM cell cultures.
                          [Fourth International Conference on AIDS,
                          June 12-16, 1988, Stockholm, Sweden, Abstract
                          #3008]
 DISEASES STUDIED/TREATED Primary HIV infection [NIAID 89 CC-62]
 CLASSIFICATION CODE      Antiretroviral [NIAID 89 CC-62]
 ADVERSE EFFECTS          According to one study,
                          3'-azido-2',3'-dideoxyuridine (AzdU) is 30
                          times less toxic to human bone marrow derived
                          granulocyte-macrophage and eryhroid precursor
                          cells than azidothymidine.  No overt toxicity
                          was observed in animal studies using rats and
                          dogs (given, respectively, 2500 and 1000
                          mg/kg orally for 28 days). In human studies,
                          maximum tolerated dose has not yet been
                          reached. AzdU has been well tolerated with
                          mild headache the only major subjective side
                          effect to date. No patient has developed
                          anemia, but one patient in a phase I trial
                          developed a grade 3 neutropenia which
                          resolved with a 50% dose decrease. [Int Conf
                          AIDS. 1990 Jun 20-23;6(3): (abstract no. S.B.
                          482)]
 CONTRAINDICATIONS        Contraindicated in pregnant or breastfeeding
                          women, or in patients with previous systemic
                          allergic reaction to the study drug. [NIAID
                          89 CC-62]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Synthetic pyrimidine
                          nucleoside analogue [Abbott-UCLA Symposium,
                          Keystone, CO April 1-6, 1987]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C9H11N5O4 [NIAID 89 CC-62]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 252.21 [NIAID 89 CC-62]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Approximately 7 mg/ml in water at
                          20 degrees C [NIAID 89 CC-62]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION:  White powder [NIAID 89
                          CC-62]
 CHEMICAL/PHYSICAL DATA   STABILITY: Approximately 7 mg/ml in water at
                          20 degrees C [NIAID 89 CC-62]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Drug supplied for injection is
                          unpreserved, sterile, isotonic solution at
                          concentration of 6.67 mg/ml, supplied in
                          glass bottles of 200 mg of drug in 30 ml of
                          ready-to-use injectable
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: solution. For oral use, drug is
                          supplied in white, capsule-shaped tablets in
                          10 and 100 mg strengths. [NIAID 89 CC-62]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY:  Intravenous injection;
                          oral. [NIAID 89-CC-62]
 MANUFACTURERS            Triton Biosciences
 REFERENCES               Chu CK, Manouilov KK, White CA, Federov I,
                          Boudinot FD. Disposition of AZT and AZdU in
                          lymph nodes of mice. Int Conf AIDS. 1994 Aug
                          7-12;10(2):202 (abstract no. PB0822).
 REFERENCES               Polis M, Davey R, Lee D, Falloon J, Kovacs J,
                          Metcalf J, Amantea M, Zurlo J, Zunich K,
                          Rosenthal Y, et al. A dose escalation study
                          to evaluate the safety, anti-viral and
                          immunological effects of
                          3'-azido-2',3'-dideoxyuridine (AZDU) in
                          patients with HIV-1 infection. Int Conf AIDS.
                          1990 Jun 20-23;6(3):206 (abstract no.
                          S.B.483).
 REFERENCES               Mitsuyasu RT, Miles SA, Wallenberg J,
                          Williams G, Marcus S. Phase I trial of
                          3'-azido-2',3'-dideoxyuride (AZDU) in
                          patients with symptomatic HIV infection. Int
                          Conf AIDS. 1990 Jun 20-23;6(3):206 (abstract
                          no. S.B.482).
 REFERENCES               Myers MW. New antiretroviral agents in the
                          clinic. Rev Infect Dis. 1990
                          Sep-Oct;112(5):944-50.
 REFERENCES               Tsai CC, Follis KE, Yarnall M, Deaver LE,
                          Benveniste RE, Sager PR. Screening for the
                          antiretroviral agents against HIV in vitro.
                          Int Conf AIDS. 1990 Jun 20-23;6(1):185
                          (abstract no. Th.A.261).
 REFERENCES               Richman DD, Darby G, Larder BA. Resistance to
                          HIV drygs. Int Conf AIDS. 1989 Jun 4-9;5:198
                          (abstract no. T.B.O.16).
 ENTRY MONTH              8906
 LAST REVISION DATE       960314
 

SOURCE: National Library of Medicine, Bethesda, MD.  Distributed by AEGIS.
